The overall objective or long-term goal of the proposed research is to discover ways to control the contractility of the uterus pharmacologically and to determine how drugs are distributed into and affect the luminal fluid of the uterus. Hopefully, these studies will relate to drug development in the areas of premature labor and contraception. The research proposal may be divided into three general categories (a) alpha adrenergic receptors; (b) oxytocin antagonists and uterine relaxants; and (c) the production, composition and distribution of substances into uterine luminal fluid. The study on uterine relaxants has as its central objective the discovery of agents or combinations of agents which produce a blockade of the effect of oxytocin on the uterus with minimal or no effects on other tissues. Also, it is hoped that drugs will be found which relax the cervix and an assay method based on the loss of uterine luminal fluid is introduced. Studies are proposed to find a means to alter the potassium content of uterine luminal fluid with the view that such information could be used to develop new contraceptive agents. A knowledge of factors affecting the distribution of substances into uterine luminal fluids could also be useful for the development of other new contraceptive agents or drugs which could act after their distribution into these fluids, eg. cancer chemotherapeutic agents. Another objective is to determine if it is possible to estimate uterine blood flow determining the rate of distribution of substances into uterine fluids. BIBLIOGRAPHIC REFERENCES: Berry, D. and Miller, J. W.: Binding of Phenoxybenzamine to Rat Platelets and Platelet Fractions. European J. Pharmacol. 31:176-184, 1975. Henkel, J. G., Portoghese, P. S., Miller, J. W. and Lewis, P.: Synthesis and Adrenergic Blocking Action of Aziridinium Ions Derived from Phenoxybenzamine and Dibenamine. Jour. Med. Chem. (accepted, August, 1975), in press.